By ELLEN GOLDBAUM

“With this treatment, we have reversed the immunosuppression that gonococcal infection normally causes and allowed an effective immune response to develop.”

Michael Russell, professor

Department of of Microbiology and Immunology

A new gonorrhea treatment, based on an anti-cancer therapy
developed by a Buffalo startup company, has successfully eliminated
gonococcal infection in female mice and prevented reinfection,
according to research published yesterday by UB scientists in the
Journal of Infectious Diseases.

Through TherapyX Inc., an early stage biotech company in
Buffalo, the UB researchers have a $300,000 Small Business
Innovation Research grant to develop the technology to treat and
prevent gonorrhea infection. UB’s Office for Science,
Technology Transfer and Economic Outreach has filed for patent
protection.

More than 100 million new gonococcal infections occur each year
around the globe, according to the World Health Organization, which
warns of a pending gonorrhea crisis due to soaring drug resistance
rates. The infection can be asymptomatic but it also can cause
extremely painful urination in men and pelvic inflammatory disease,
which can lead to infertility and ectopic pregnancy, in women. It
also may make individuals more susceptible to infection with
HIV/AIDS.

“We developed the concept that gonococcal infection seems
to inhibit specific adaptive immune responses, which is, in part,
why people can become infected with it multiple times,”
explains Michael W. Russell, professor of microbiology and
immunology in the UB School of Medicine and Biomedical Sciences and
senior author on the paper. “It turns out that gonococcal
infection very cleverly controls the immune system, inducing
responses the bacterium can fight and suppressing the responses
that it cannot fight.”

In considering how to modify the immune response to gonococcal
infection, Russell became intrigued with an anti-cancer therapy
being developed by a medical school colleague.

Nejat K. Egilmez, professor of microbiology and immunology and a
co-author on the current paper, developed NanoCap, a
sustained-release nanoparticle treatment that uses Interleukin-12,
a cytokine or protein that helps stimulate an immune response
against tumors that normally suppress immunity. Egilmez co-founded
TherapyX Inc. to commercialize this and other drug
formulations.

“We had the idea that maybe these IL-12 microspheres that
they were developing against tumors could be used to generate an
immune response against gonococcal infection as well,” says
Russell. “This research proves that they can.”

The current study describes how the IL-12 microspheres,
administered intravaginally in mice, resulted in the development of
a specific adaptive immune response—development of antibodies
specific to N. gonorrhoeae—and clearance of the
infection within days. One month later, attempts to reinfect these
mice with the bacterium failed, demonstrating that the animals had
retained the ability to fight reinfection.

“With this treatment, we have reversed the
immunosuppression that gonococcal infection normally causes and
allowed an effective immune response to develop,” says
Russell. “It could be argued that when the IL-12 microspheres
are administered this way, they serve as an adjuvant that, in
effect, converts the gonococcal infection into a live vaccine, thus
essentially vaccinating the very population that is at risk for
repeat infections.”

And because it may circumvent the growing resistance of this
bacterium and others to antibiotics, this treatment method also may
open up new approaches for the development of nonresistant
treatments for other infectious diseases, Russell says.

“Here, we are delivering cytokines locally right to the
site of infection,” he says. “If we can use this method
to teach the immune system to generate the right kind of response
to other recalcitrant infections, then we could have a new approach
to treat a range of infectious diseases without stimulating drug
resistance.”

The immunity developed in the mice lasted for one month. Russell
plans to see if the immunity can last longer in mice and then,
ultimately, test it in humans.

The first author on the paper is Yingru Liu, UB research
assistant professor in the Department of Microbiology and
Immunology and a principal investigator at TherapyX. All three
authors are researchers in UB’s Witebsky Center for Microbial
Pathogenesis and Immunology.

The work was funded by the National Institute of Allergy and
Infectious Diseases at the National Institutes of Health and a
grant from The John R. Oishei Foundation of Buffalo.

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